TY - JOUR
T1 - Curcumin prevents corticosterone-induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway
AU - Xu, Ying
AU - Li, Shan
AU - Vernon, Matthew M.
AU - Pan, Jianchun
AU - Chen, Ling
AU - Barish, Philip A.
AU - Zhang, Yuan
AU - Acharya, Abhinav P.
AU - Yu, Jie
AU - Govindarajan, Subramaniam S.
AU - Boykin, Erin
AU - Pan, Xiaoyu
AU - O'Donnell, James M.
AU - Ogle, William O.
PY - 2011/9
Y1 - 2011/9
N2 - Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT1A, 5-HT2A and 5-HT4, but 5-HT1B, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT1A and 5-HT4 receptors, but not for the 5-HT2A receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT 1A receptor antagonist p-MPPI or 5-HT4 receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.
AB - Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT1A, 5-HT2A and 5-HT4, but 5-HT1B, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT1A and 5-HT4 receptors, but not for the 5-HT2A receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT 1A receptor antagonist p-MPPI or 5-HT4 receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.
KW - 5-HT receptors
KW - cAMP
KW - corticosterone
KW - curcumin
KW - neuronal plasticity
UR - http://www.scopus.com/inward/record.url?scp=80051786861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051786861&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2011.07356.x
DO - 10.1111/j.1471-4159.2011.07356.x
M3 - Article
C2 - 21689105
AN - SCOPUS:80051786861
SN - 0022-3042
VL - 118
SP - 784
EP - 795
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -